In this project we are characterizing circulating growth hormone species in conditions of abnormal human growth. A two stage homologous radioreceptor assay for human growth hormone has been developed utilizing 1M-9 lymphocytes. It has validated and will be applied to sera of patients with growth failure, growth with inappropriately low growth hormone by radioimmunoassay and to patients with acromegaly. When significant discrepancies are found growth hormone will be separated from larger serum proteins by gel filtration through Sephadex G-100. The isolated growth hormone will be compared to known growth hormone subspecies in respect to molecular size and isoelectric point (isoelectric focusing). We are continuing our studies of growth hormone releasing factors. Most of the effort for the coming year will be devoted to purification of a growth hormone releasing factor from a large carcinoid tumor obtained from a patient with a metastatic carcinoid tumor. We have confirmed Frohman's observation that this particular tumor does contain a rather large polypeptide which can release growth hormone from isolated rat pituitary cells. Further purification and characterization of this peptide are in progress. Clinical studies of growth hormone and prolactin hypersecretion are being conducted in an attempt to recognize additional cases where hypersecretion is the result of circulating releasing factor. Our principal interest will be the possible secretion of such releasing factors by ectopic tumors.